The long-term objective of this proposed research is to obtain a better understanding of the metabolism of selenium (Se) in humans with the use of stable isotopes. The specific aims of this study are to determine the relationship of various indices of Se status (blood components) to the size of the selenite exchangeable metabolic pool (Se-EMP); establish the relationship of dietary Se intake to excretion of urinary trimethyl selenonium (TMSe); and determine the influence of Se restriction on the rate of depletion of Se-EMP. This work is proposed to be done with stable isotopes of Se with human subjects in China. Populations have been identified which are deficient in Se, with normal Se intakes and with subtoxic levels of Se intake. These three populations will be used to determine the influence of Se status on turnover of selenoproteins and on the Se-EMPs. Patients from the subtoxic area will be taken to the Se deficient area (Dechang) to study the effects of Se restriction on the Se- EMP and turnover of Se containing proteins. After the isotopes are given to the subjects, blood and urine will be collected at various times afterwards. The turnover of Se in plasma selenoprotein P, glutathione peroxidase (GPX), and albumin will be determined from the isotope content of these fractions with respect to various times after isotope administration. These blood components are proposed to be separated by column chromatography. The stable isotope content of total Se and TMSe excretion will be determined in the urine. From the Se content the Se-BMPs can be calculated. It is anticipated that the proposed research will provide additional information on the metabolism of Se as related to certain human metabolic disorders such as cancer and heart disease (Keshan disease).